NCCN Guidelines® Updates: Hepatobiliary Cancers

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hepatobiliary Cancers, published in this issue (page 541), include the latest updates. To assist readers interested in noting how the guidelines were updated, highlights of major changes pertaining to the portion of the guidelines published in this issue are provided below. To view the most recent version of the guidelines, visit

Updates in Version 2.2021 from Version 5.2020 include:


  1. The Principles of Radiation Therapy (HCC-F) has been separated out from the Principles of Locoregional Therapy (HCC-E).


  1. Screening:
    1. 2nd column was revised: “Ultrasound ± Alpha fetoprotein” was changed to “Ultrasound + Alpha fetoprotein.”
    2. Footnote “d” was revised: “…outcomes for patients with HCC in the setting of NAFLD/HBV/HCV cirrhosis when the NAFLD/HBV/HCV is successfully treated.”
    3. Footnote “j” was removed: “AFP is considered optional for screening.” (See Principles of Imaging, HCC-A)


  1. Workup: Multidisciplinary evaluation:
    1. 9th bullet was revised: “Abdominal/pelvic CT or MRI with contrast, if not previously done or needs updating.”
    2. New 10th bullet was added: “Consider referral to a hepatologist.”
    3. Third option in last column was revised: “Liver-confined disease, inoperable by performance status, or comorbidity, local disease only or with minimal or unknown extrahepatic disease.” (Also on HCC-6)


  1. Surgical Assessment: After UNOS criteria, 2nd bullet was added: “Extended criteria.”
  2. Surveillance: 4th bullet was revised: “...for carriers of hepatitis if not previously done.”
  3. Footnote “x” was revised, “Extended criteria/downstaging protocols are available at selected centers and through UNOS...”
  4. Footnote “dd” was revised: “Multiphasic abdominal/pelvic MRI or multi-phase CT scans for liver assessment, are recommended. Consider CT chest and CT/MRI pelvis (See Principles of Imaging, HCC-A).” (Also on HCC-5)


  1. Treatment:
    1. After “Not a transplant candidate,” the treatment options were divided into two separate pathways:
      1. Upper pathway: Locoregional therapy preferred listed with corresponding options.
      2. Lower pathway: Includes the options of clinical trial, systemic therapy, and best supportive care. (Also HCC-6)
  2. Surveillance: 4th bullet was added: “Consider early imaging per local protocol.”


  1. Metastatic disease or Extensive liver tumor burden pathway:
    1. Recommendation was revised to “Consider Biopsy to confirm metastatic disease for histologic confirmation if not previously done.”

HCC-G (1 of 2)

  1. First-Line Therapy:
    1. Preferred Regimens: Sorafenib and lenvatinib were moved under, “Other Recommended Regimens.”
    2. Under Useful in Certain Circumstances: The nivolumab recommendation was revised to include “(Child-Pugh Class A or B).”
  2. Subsequent-Line Therapy If Disease Progression:
    1. The following were moved from the list of “Options” to under “Other Recommended Regimens”:
      1. Nivolumab (Child-Pugh Class A or B)
      2. Nivolumab + ipilimumab (Child-Pugh Class A only)
      3. Pembrolizumab (Child-Pugh Class A only) (category 2B)
  3. Footnotes:
    1. Footnotes “c” and “k” were added.
    2. Footnote “j” was revised: “For patients who have not been previously treated with a checkpoint inhibitor because there is a lack of data for subsequent use of immunotherapy in patients who have previously been treated with a checkpoint inhibitor.”
    3. Footnote “I” was revised: “The data reflect use on or after sorafenib in patients who previously tolerated sorafenib at a dose of at least 400 mg per day.”

The goal of the NCCN Guidelines® Updates is to provide readers with important changes that the NCCN Guidelines Panel has incorporated into the algorithm since it was last published. For a more complete detailing of the updated guideline‘s modifications, access the NCCN Guidelines in this issue or, for the complete and most up-to-date version, at

Note: The addition of new language is indicated in italics. Wording that was removed from the previous update is indicated in strikeout.

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